The search for an effective mode of therapy for the prevention of sudden cardiac death has led to widespread investigation of the basic mechanisms underlying disorders of cardiac rhythm. Recent years have witnessed the accumulaton of a large body of evidence implicating the central nervous system as an important determinant in the genesis of cardiac arrhythmias. The purpose of the proposed pharmacol gic and electrophysiologic studies is to assess the extent to which the protective effect of commonly used antiarrhytmic agents results from or is mediated by a primary effect on the central nervous system rather than a direct myocardial effect. The studies are designed to evaluate the efficacy of diphenylhydantoin and propranolol in preventing and reversing ventricular arrhythmias induced by digitalis intoxication and myocardial ischemia when the drugs are injected in small doses directly into the cerebrospinal fluid of experimental animals or administered selectively to the cerebral circulation. In conjunction with these basic pharmacologic studies, electrophysiologic studies utilizing bipolar plunge wire electrode recordings and programmed cardiac stimulation will be performed to determine the effect of drugs introduced directly into the central nervous system on conduction and refractories within various cardiac tissues and to compare these findings with observations made following systemic administration of the drug. These studies will provide more precise information about the sites and mechanisms of action of antiarrhythmic drugs and should increase our knowledge of the role of the central nervous system in influencing vulnerability to cardiac arrhythmias. The studies will provide new information about the extent to which changes in standard electrophysiologic parameters observed after systemic administration of antiarrhythmic drugs result from CNS-mediated as opposed to direct myocardial effects. These studies will also provide new information about the extent to which the antiarrhythmic effect of a drug is linked to and dependent upon observable changes in standard electrophysiologic parameters in various cardiac tissues.